Patient-reported outcome assessment of inflammatory arthritis patient experience with intravenously administered biologic therapy

Objective: To evaluate patient perspectives regarding utilization of intravenous (IV) therapy for inflammatory arthritis (IA). Methods: This was a single-center, non-interventional, patient questionnaire-based study of adult IA patients currently receiving IV biologics. At a single visit, patients completed the questionnaire comprising 30 questions centered on their experience receiving an intravenously administered therapy to treat their IA. The questionnaire included questions on patient demographics, disease characteristics, and previous biologic treatment for IA (subcutaneous [SC] and IV). Patients rated their level of agreement with statements regarding satisfaction with current IV biologic therapy and potential advantages and disadvantages of IV biologic therapy using a 5-point Likert scale (1= strongly disagree, 5= strongly agree). Results: One hundred patients were enrolled and completed the survey; 66% were female and the mean age was 58 years. Before IV treatment, 97% of patients received information regarding therapy options. Ninety patients ranked their satisfaction with current IV therapy as 4 or 5. The proportion of patients with an “extremely favorable” perception of IV therapy increased from 33% to 71% following initiation of their current medication. Thirty-one patients had previously received SC therapies to treat their IA. Conclusion: These results demonstrated an overall favorable perception of IV therapy among this patient population. Patients previously treated with SC therapy also had a positive shift in the perception of IV therapy after initiating IV therapy. Patients’ perception and preference for treatment options should be highly considered by the treating physician during or as part of a shared decision-making process. © 2017 Gaylis et al

Factors Associated With Short- and Long-Term Outcomes of Therapy for Crohn’s Disease

Background & AimsOur post hoc analysis assessed the association of early (at weeks 26–30) clinical, endoscopic, biologic, and pharmacokinetic outcomes with corticosteroid-free remission at week 50 (CSFR50); CSFR50 was observed in 55.2% and 65.4% of patients treated with infliximab, alone or in combination with azathioprine, respectively.MethodsWe analyzed data from 203 patients: 96 received infliximab monotherapy and 107 received combination therapy. Receiver operating characteristic analysis was used to set cut-off points for the week 30 trough serum infliximab concentration (SIC30) and percentage change, from baseline, in the C-reactive protein (CRP) level at week 26, to predict CSFR50. Univariate and multivariate procedures analyzed predictive parameters of CSFR50 (odds ratio [OR] and 95% confidence interval [CI]). Mucosal healing (MH, zero ulcers) and CRP normalization (<8.0 mg/L) also were assessed.ResultsTrough SIC30 was higher in patients with than without CSFR50. Patients given combination therapy had higher trough SIC30s than those given monotherapy. Median trough SIC30 was significantly higher in patients with than without CSFR50 among those on infliximab monotherapy (2.14 vs 0.80 μg/mL; P = .006), but not for those on combination therapy (3.56 vs 3.54 μg/mL; P=.31). In patients with increased baseline levels of CRP (n = 120), corticosteroid-free remission at week 26 (CSFR26) (OR, 4.09; 95% CI, 1.65–10.11), and trough SIC30s of 3.0 μg/mL or greater (OR, 3.20; 95% CI, 1.38–7.42) were associated significantly with CSFR50. In patients evaluable for MH (n = 123), trough SIC30s of 3.0 μg/mL or greater (OR, 3.34; 95% CI, 1.53–7.28) and CRP normalization (OR, 2.69; 95% CI, 1.10–6.54) were associated significantly with MH at week 26 (MH26). Furthermore, CSFR26 (OR, 4.43; 95% CI, 1.81–10.82) and MH26 (OR, 3.01; 95% CI, 1.33–6.81) were associated significantly with CSFR50.ConclusionsTrough SIC30 is associated positively with MH26; CSFR26 and MH26 are independent predictors of CSFR50. Trough SIC30 of 3.0 μg/mL or greater early during maintenance treatment is an important determinant of clinical and endoscopic Crohn’s disease outcomes. ClinicalTrials.gov number, NCT00094458

Clinical response to golimumab in rheumatoid arthritis patients who were receiving etanercept or adalimumab: results of a multicenter active treatment study

<p><b>Objective:</b> Evaluate the efficacy and safety of subcutaneous (SC) golimumab + methotrexate (MTX) in patients with active rheumatoid arthritis (RA) despite etanercept + MTX or adalimumab + MTX therapy and evaluate whether intravenous (IV) golimumab could rescue patients who were nonresponders to SC golimumab.</p> <p><b>Methods:</b> In this multicenter, assessor-blinded, active-switch study of patients with RA (<i>n</i> = 433) with inadequate response to etanercept or adalimumab + MTX, patients continued MTX and received open-label SC golimumab 50 mg every 4 weeks through week 12. DAS28-ESR good responders at week 16 continued open-label SC golimumab through week 52 (Group 1); nonresponders were randomized to double-blind golimumab SC 50 mg (Group 2-SC) or IV 2 mg/kg (Group 2-IV). Week 14 ACR20 was the primary endpoint; assessments continued through week 52 and for patients in the voluntary long-term extension through week 76. A major secondary endpoint was the proportions of patients with ACR20 response at week 52 relative to week 16 in Group 2-SC and Group 2-IV.</p> <p><b>Results:</b> At week 14, 34.9% (<i>p</i> < 0.001) achieved an ACR20. At week 52, patients in Group 1 (<i>n</i> = 75) achieved an ACR20 (62.7%). In Groups 2-SC (<i>n</i> = 91) and 2-IV (<i>n</i> = 184), 13.2% and 9.2% had an ACR20 at week 52 relative to week 16, with no significant difference between the randomized groups; 42.9% and 47.8% achieved DAS28-ESR response relative to week 0. Through week 16, 4.6% of patients had a serious adverse event. No differences in the rates or types of adverse events were observed between SC and IV golimumab from weeks 16 to 52. The trial limitations included a higher than expected discontinuation rate as a result of a programming error.</p> <p><b>Conclusion:</b> SC golimumab + MTX significantly suppressed disease activity in RA patients with inadequate response to etanercept and/or adalimumab + MTX. Patients randomized to Groups 2-SC and 2-IV had lower response rates than Group 1, with no difference between SC or IV mode of administration. The safety profile with IV golimumab was comparable to that established with SC golimumab.</p> <p><b>Trial registration:</b> NCT01004432, EudraCT 2009-010582-23.</p

Change in Erythrocyte Mean Corpuscular Volume During Combination Therapy with Azathioprine and Infliximab Is Associated with Mucosal Healing: A Post hoc Analysis from SONIC.

International audienceThe adequacy of exposure of purine analogs as measured by 6-thioguanine nucleotides concentrations in the setting of combination therapy remains poorly understood. The aim of this study was to investigate the relationship between the mean corpuscular volume (MCV) value (as a surrogate marker of 6-thioguanine nucleotides concentration) and Crohn's disease outcomes in the setting of combination therapy with infliximab. The SONIC trial was a randomized controlled trial comparing infliximab to azathioprine and to infliximab plus azathioprine in 508 Crohn's disease patients. An increase of at least 7 femtoliter (fL) of the MCV (ΔMCV) was used for statistical analysis. At week 26, the mean increase of MCV was similar among patients treated with azathioprine alone (mean of 7.9 fL) or in combination with infliximab (mean of 8.5 fL). In the azathioprine group, 63.6% of patients with ΔMCV >7 were in steroid-free clinical remission at week 26 as compared with 33.3% of patients without ΔMCV >7 (P = 0.0046). In the combination therapy group, ΔMCV above 7 was associated with mucosal healing (75.0% for ΔMCV >7 versus 47.1% for ΔMCV <7, P = 0.0172) but not with steroid-free clinical remission. Patients with a ΔMCV above 7 were more likely to have infliximab trough level above 3 μg/mL at week 30 (68.4% versus 38.8% for ΔMCV <7, P = 0.0032). These results suggest that ΔMCV above 7 (which is a surrogate for a higher 6-thioguanine nucleotides concentration) leads to improved Crohn's disease outcomes, even when combined with infliximab. It also suggests the possibility that a lower azathioprine exposure might be less effective in combination therapy

Infliximab, azathioprine, or combination therapy for Crohn's disease

BACKGROUND: The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown. METHODS: In this randomized, double-blind trial, we evaluated the efficacy of infliximab monotherapy, azathioprine monotherapy, and the two drugs combined in 508 adults with moderate-to-severe Crohn's disease who had not undergone previous immunosuppressive or biologic therapy. Patients were randomly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0, 2, and 6 and then every 8 weeks plus daily oral placebo capsules; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the standard schedule; or combination therapy with the two drugs. Patients received study medication through week 30 and could continue in a blinded study extension through week 50. RESULTS: Of the 169 patients receiving combination therapy, 96 (56.8%) were in corticosteroid-free clinical remission at week 26 (the primary end point), as compared with 75 of 169 patie

Validation of endoscopic activity scores in patients with Crohn's disease based on a post hoc analysis of data from SONIC

Mucosal healing might alter midterm and long-term outcomes of patients with Crohn's disease (CD) and has become an important end point in clinical trials. However, the minimal degree of mucosal improvement (endoscopic response) required to alter midterm outcomes is not known. We aimed to determine the best definition of endoscopic response by evaluating data on the Simple Endoscopic Score for Crohn's Disease (SES-CD) and the Crohn's Disease Endoscopic Index of Severity (CDEIS) from the Study of Biologic and Immunomodulator Naive Patients in Crohn's Disease (SONIC trial). We analyzed data from 172 patients who participated in the SONIC trial, were found to have endoscopic lesions at baseline, and underwent a second endoscopic examination at week 26 of treatment with infliximab, azathioprine, or both. Mucosal healing was defined as absence of ulcers. A central reader calculated SES-CD and CDEIS results. Different cutoff values were set for endoscopic response based on the SES-CD or CDEIS. The diagnostic ability of these different cutoff values was evaluated using receiver operating characteristic (ROC) curves, positive likelihood ratios (PLR), and negative likelihood ratios (NLR). Corticosteroid-free clinical remission (CFREM) at week 50 was used as a binary classifier. Based on analyses of ROC curves, PLR, and NLR, endoscopic response was defined as a decrease from baseline in SES-CD of at least 50%. At week 26, mucosal healing and endoscopic response were achieved in 48% and 65% of patients, respectively. Mucosal healing at week 26 was associated with CFREM at week 50, with 56% sensitivity, 65% specificity, a PLR of 1.60, and an NLR of 0.67. Endoscopic response at week 26 was associated with CFREM at week 50, with 74% sensitivity, 48% specificity, a PLR of 1.42, and an NLR of 0.54. Endoscopic response, defined as a decrease from baseline in CDEIS of at least 50%, yielded similar results. In patients with CD, mucosal healing and endoscopic response (defined as a decrease from baseline in SES-CD or CDEIS of at least 50%) at week 26 of treatment identified those most likely to be in CFREM at week 50. The ability of the proposed endoscopic response cutoff value to predict midterm CFREM should be validated in an independent, prospective cohort. Its correlation with changes in long-term disease progression still needs to be demonstration. ClinicalTrials.gov, Number: NCT0009445

Infliximab is not associated with increased risk of malignancy or hemophagocytic lymphohistiocytosis in pediatric patients with inflammatory bowel disease

BACKGROUND AND AIMS: Immunosuppressive therapy for inflammatory bowel disease (IBD) in pediatric patients is thought to increase the risk of malignancy and lymphoproliferative disorders, including hemophagocytic lymphohistiocytosis (HLH). We compared unadjusted incidence rates of malignancy and HLH in pediatric patients with IBD exposed to infliximab (IFX) with patients not exposed to biologics and calculated standardized incidence ratios (SIRs). METHODS: We collected and analyzed data from 5766 participants in a prospective study of long-term outcomes of pediatric patients with IBD (NCT00606346), from May 31, 2007 through June 30, 2016. Patients were 17 years old or younger and had Crohn's disease, ulcerative colitis, or IBD-unclassified with 24,543.0 patient-years of follow-up. We estimated incidence rates for malignancy and HLH as events/1000 patient-years of follow-up. We calculated age-, sex-, and race-adjusted SIRs, with 95% confidence intervals (CIs), using the Surveillance, Epidemiology, and End Results Program (SEER) database. RESULTS: Thirteen of the 15 patients who developed a malignancy and all 5 of the patients who developed HLH had been exposed to thiopurines; 10 patients with malignancy had also been exposed to a biologic agent. Unadjusted incidence rates showed no increased risk of malignancy (0.46/1000 patient-years) or HLH (0.0/1000 patient-years) in patients exposed to IFX as the only biologic vs those unexposed to biologics (malignancy: 1.12/1000 patient-years; HLH: 0.56/1000 patient-years). SIRs did not demonstrate an increased risk of malignancy among patients exposed to IFX (SIR, 1.69; 95% CI, 0.46-4.32) vs patients not exposed to a biologic agent (SIR, 2.17; 95% CI, 0.59-5.56), even when patients were stratified by thiopurine exposure. CONCLUSIONS: In determination of age-, sex-, and race-adjusted SIRs using data from a large clinical study and the SEER database, we found that IFX exposure did not associate with increased risk of malignancy or HLH in pediatric patients with IBD. Thiopurine exposure is an important precedent event for the development of malignancy or HLH in pediatric patients with IBD